This proposal is concerned with quantitatively defining the relationships between the molecular organization and the fundamental ionic permeability processes of bilayers. The intrinsic electrochemical and physical properties of lipids and polypeptides observed in the well controlled circumstances of monolayers are believed to be relatable to the behavior of the same molecular combinations in oriented bimolecular lipid membranes. Surface tensions and surface potentials of mixtures of lipids and other molecules will be determined systematically in monolayers (air/water and oil/water interface). Such characteristics will be related to the ionic permeability and molecular organization of bilayers in order to test this hypothesis. Specifically, molecular area, dipole moments and net charge of lipids such as cholesterol, monoolein and phospholipids will be used in an attempt to predict and identify their distributions within bilayer membranes. The validity of these predictions will be tested directly using techniques previously developed for probing the structure of lipid bilayer membranes. The study will be extended to include the influence of functional additives (ion carriers, channel formers) for the purpose of establishing precise structure-function relationships for membrane transport processes. The electrophysiological and electrochemical studies will be complemented by electron microscopic diffraction studies of the same systems in order to establish clear links between membrane ultrastructure and function. A convergence of surface chemical, electrophysiological and ultrastructural informations from studies of well defined model systems can be expected to establish a framework for a detailed understanding of complex membrane processes such as nerve membrane excitability.